13-98831698-T-A

Variant names:

• chr13-98831698-T-A
• NM_001366683.2:c.4403A>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001366683.2(DOCK9):​c.4403A>T​(p.Glu1468Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DOCK9 NM_001366683.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.64

Genes affected

DOCK9 (HGNC:14132): (dedicator of cytokinesis 9) Enables cadherin binding activity. Predicted to be involved in positive regulation of GTPase activity. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.79

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK9	NM_001366683.2	c.4403A>T	p.Glu1468Val	missense_variant	Exon 40 of 53	ENST00000682017.1	NP_001353612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK9	ENST00000682017.1	c.4403A>T	p.Glu1468Val	missense_variant	Exon 40 of 53		NM_001366683.2	ENSP00000507034.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 14, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.4337A>T (p.E1446V) alteration is located in exon 40 (coding exon 40) of the DOCK9 gene. This alteration results from a A to T substitution at nucleotide position 4337, causing the glutamic acid (E) at amino acid position 1446 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	.;.;.;.;T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D;D;D;D;D
M_CAP	Benign	0.070	D
MetaRNN	Pathogenic	0.79	D;D;D;D;D
MetaSVM	Benign	-0.63	T
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-4.4	.;D;.;D;D
REVEL	Uncertain	0.44
Sift	Uncertain	0.0080	.;D;.;D;D
Sift4G	Uncertain	0.0060	.;D;D;.;D
Polyphen		0.85, 0.99	.;P;.;D;.
Vest4		0.86, 0.90
MVP		0.77
MPC		1.1
ClinPred		0.99	D
GERP RS		5.8
gMVP		0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-99483952;